Genomics and Molecular Medicine, CSIR Institute of Genomics and Integrative Biology, Delhi, India.
Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
Indian Pediatr. 2021 May 15;58(5):445-451.
Information on etiology of congenital nephrotic syndrome in non-Caucasian populations is limited. This study aimed to determine the genetic basis of congenital nephrotic syndrome in Indian patients.
In this observational, cross-sectional study, whole exome sequencing was performed on samples from all children diagnosed with congenital nephrotic syndrome, presenting at centers collaborating in a nationwide registry and biorepository. Analysis was targeted to focus on reported or novel, pathogenic or likely pathogenic variants in 89 genes implicated in etiology of nephrotic syndrome. Sanger sequencing was used to confirm disease-causing variants in patients and allelic segregation of compound heterozygous variants in samples from parents. Inheritance of a shared haplotype was analyzed among ten individuals carrying the most common variant.
During 2017-2019, 34 patients with congenital nephrotic syndrome were screened. Consanguinity and similar illness in siblings were reported in eleven patients each. Homozygous or compound heterozygous, pathogenic or likely pathogenic variants were found in NPHS1 in 24 cases, including two novel variants. One patient each had homozygous pathogenic or likely pathogenic known or novel variant in NPHS2, PLCE1, OSGEP and LAMB2 genes. Patients with OSGEP and LAMB2 mutations had phenotype typical of Galloway Mowat and Pierson syndromes, respectively. Three variants in NPHS1 were common to 16 individuals. One reported variant in exon 19 (c.2600G>A; p.Gly867Asp) appears to share a common founder.
A genetic cause was determined for 82.4% patients with congenital nephrotic syndrome. Variants in NPHS1 are most common in Indian patients and founder mutations might be present.
非高加索人群先天性肾病综合征病因方面的信息有限。本研究旨在确定印度患者先天性肾病综合征的遗传基础。
在这项观察性、横断面研究中，对在参与全国登记处和生物库的合作中心确诊为先天性肾病综合征的所有儿童的样本进行了全外显子组测序。分析靶向针对 89 个与肾病综合征病因相关的报告或新的、致病性或可能致病性的基因中的变异。对患者进行 Sanger 测序以确认致病变异，对来自父母的样本进行复合杂合变异的等位基因分离。在携带最常见变异的 10 个人中分析共享单倍型的遗传。
在 2017-2019 年期间，对 34 例先天性肾病综合征患者进行了筛查。有 11 例患者报告存在近亲结婚和同胞相似疾病，24 例患者发现 NPHS1 中的纯合子或复合杂合子、致病性或可能致病性变异，包括 2 个新变异。1 例患者各有 NPHS2、PLCE1、OSGEP 和 LAMB2 基因中的纯合子致病性或可能致病性的已知或新变异。携带 OSGEP 和 LAMB2 突变的患者分别表现出典型的 Galloway-Mowat 和 Pierson 综合征表型。NPHS1 中的 3 个变异在 16 个个体中是共同的。一个报告的外显子 19 中的变异（c.2600G>A；p.Gly867Asp）似乎共享一个共同的祖源。
82.4%的先天性肾病综合征患者确定了遗传病因。NPHS1 中的变异在印度患者中最常见，可能存在创始突变。
